This investigation is concerned with the analysis of polymorphic enzyme phenotypes in tumor and normal tissue samples derived from the same patients. We have analyzed the isozyme phenotypes of seven polymorphic enzyme systems (phosphoglucomutase 1,3, esterase D, adenylate kinase, glyoxalase, fucosidase, and phosphogluconate dehydrogenase) in approximately 110 matched sets of tumor and normal tissue samples. This analysis has been undertaken to determine if the extensive loss of functional gene expression we have observed in cultured human tumor cells occurs in in vivo tumors and to determine to what extent it is affected by the growth of tumor cells in culture. Methods used in this study include starch, polyacrylamide and cellulose acetate gel electrophoresis, and isoelectric focusing in polyacrylamide and agarose gels. The majority of tumor samples presently collected include breast, lung, and colon carcinomas. Attempts will be made to extend the range of tumor types to be surveyed in the next year. Preliminary data suggest that hemizygosity occurs less frequently in primary tumors than it does in human tumor cells grown in culture. However, at present it has not always been possible to determine whether the possible loss of heterozygosity in tumor cells is masked by the presence of both isozymes in the associated normal tissues and red cells. (B)